Showing posts with label journal of biochemistry. Show all posts
Showing posts with label journal of biochemistry. Show all posts

Monday, 8 May 2017

E-Pharmacophore Model Assisted Discovery of Novel Antagonists of nNOS



Alzheimer’s disease (AD) is the most common form of dementia characterized clinically with progressive cognitive decline and neuronal loss. Pathologically, AD affected brain shows accumulation of β-amyloid (Aβ) plaques and neurofibrillary tangles formed by the hyper phosphorylation of tau protein. Recent studies indicate that mitochondrial dysfunction, a pathological featurethat can be detected early in AD. Nitric oxide synthases (NOS) are a family of enzymes catalyzing the production of nitric oxide (NO), which functions as neuronal signalingmolecule. Altered expression of nNOS by the Aβ stimulus results in the formation of peroxy nitrite and reactive oxygen species. These peroxy-nitrite, nitrosylates the cytoplasmic protein tau and phosphorylates GSK-3β.

E-Pharmacophore Model
Nitrosylation of tau protein results in structural and conformational change of tau protein ensuring the destabilization of microtubule. This leads to dissociation of tau protein from microtubule and oligomerization of tau occurs to form neuro-fibrillary tangles (NFT’s). These tangles forms a physical road blocks within the neuronal cells and interrupts the neurotransmitter signaling.

Wednesday, 18 January 2017

p53 Mutation: Critical Mediator of Therapy Resistance against Tumor Microenvironment



GBM, a grade IV glioma classified by World Health Organization, is considered highly malignant, vascular and invasive subtype. Hypoxia and neovascularization are signature histopathologic features of GBM, which is most lethal during first year after initial diagnosis despite surgical resection and other standard therapies. Temozolomide chemotherapy andradiotherapy against GBM tumor cells have led to a significant improvement intumor growth and patient survival in newly diagnosed and recurrent GBM. The survival advantage conferred by temozolomide chemotherapy is associated with methylation of the promoter region of the gene encoding O6-methylguanine DNAmethyltransferase (MGMT). Both tumor protein p53 (TP53) and MGMT are involved in DNA repair after chemotherapy or radiotherapy, which may contribute to drug resistance. In addition, tumor cells acquiring several mutations during tumor progression could contribute to therapy resistance in GBM.

p53 Mutation

Many different types of cancer including GBM show a high incidence of TP53 mutations, leading to the stabilization and overexpression ofmutant p53 proteins. Mutant p53 have both lost wild-type p53 tumor suppressor activity and gained functions that help to contribute to tumor progression . 

Wednesday, 4 January 2017

A Semi-Empirical Approach to Estimate Kinetic Parameters for the Batch and Continuous Settling of Flocculating Yeast Slurries



Increased productivity is one of the most important objectives in continuous production of ethanol. It is generally accepted that a high concentration of yeast favors an increased ethanol yield of the fermentation process . Several techniques that promote the accumulation ofbiomass in fermenters have been used in continuous fermentation processes, including cell immobilization in polymeric matrices and cell recycle by centrifugation or filtration through membranes. Good performances have been reported for processes using immobilized cells; however, procedures and materials involved in this technique are inaccessible to a large number of small industrial units . Centrifugation and filtration equipments are extremely expensive and prone to mechanical problems; the use of these equipments is limited due to high investment and maintenance costs. Since yeast separation by conventional methods is an expensive operation in alcoholic fermentation plants, alternative separation techniques using cheaper equipment such as hydrocyclones and settlers have been investigated aiming to reduce the costs involved in ethanol production.

Flocculating Yeast Slurries

Although solid particles can settle under the action of a centrifugal force, gravitational sedimentation is understood as the settling of particles within a fluid under the force of gravity. The factors that controlthe settling velocity are the solids concentration in the slurry, the densities of solid and liquid, the size and shape of the particles and the viscosity of the medium. However, the most important factors are the particle size and particle density.

Wednesday, 19 October 2016

Jasmonic Acid: Genetic Pathway, Signal Transduction and Action in Plant Development and Defence



Jasmonic acid (JA) is one of the most signaling phytohormones which play an essential role in plant development and response to biotic and abiotic stresses. It plays a key regulatory role in root elongation, pollen production, germination, fruit ripening, plant senescence. Additionally, it activates plant defenses against pests, pathogens and abiotic stress. Jasmonic acid and its derivative methyl jasmonate are abundant in plant cellsand have a physiological signaling mechanism. Recently, jasmonates have been reported to be the active forms precursors comprising certain amino acid conjugates. Jasmonates are generally synthesized and accumulated upon environmental or developmental stimuli. Jasmonate signal transduction process is regulated by a signaling mechanism embracing certain repressor proteins which control different transcription factors regulating the expression of jasmonate responsive genes.

Jasmonic Acid

The first step of JA synthesis takes place in chloroplasts membranes, where a phospholipase generates both of α-linolenic acid and hexadecatrienoic acid from membrane phospholipids. JAs synthesisoccurs generally from the α-linolenic acid precursor through the octadecanoidpathway. Chloroplastic 13-lipoxygenase oxidizes αLA forming the 13-hydroperoxy derivative of linolenic acid. The Arabidopsis genome comprises six genes encoding lipoxygenases. Three of such genes (LOX2, LOX3 and LOX4) regulate JA production. The next steps of JA synthesis occur in the peroxisome.

Wednesday, 12 October 2016

Salivary Progesterone as a Biomarker in Pregnancy



Progesterone is considered as the pregnancy hormone. Already in 1958 Short was able to determine progesterone in blood and found that during pregnancy its levels increase from <0.1 μg/100 mL (nonpregnant) up to 87 μg/100 ml. In addition, Eton and Short found that in early abortion or premature delivery the concentration of progesterone was relatively low, which finding were confirmed by Wiest for fetal death. The role of progesteroneduring pregnancy includes the preparation of the uterus for implantation, to keep the uterus quiescent during gestation and lower immune responses of the mother. Initially, it is produced by the corpus luteum and after about 8 weeks by the placenta. It is suggested that a decline in progesterone levels facilitate the onset of labor and triggers milk production. Premature labour is characterized by progesterone concentrations lower than normal and may be prevented by the administration of progesterone, 17OHprogesterone or 17-hydroxyprogesterone-caproate. An update of this subject was given in a lecture during 14th Annual Symposium at the University of Illinois, Chicago, by Grobman, October 31, 2014.

Salivary Progesterone

The drop in progesterone levels as a trigger to the onset of labor has been assessed in sheep and other mammals and called‘P-withdrawal’. Attempts to confirm this mechanism in humans has been hampered by the fact that repeated blood sampling is too stressful and not feasible in situations that there is no health threat or medical indication.